Transient deoxyhemoglobin formation as a contrast for perfusion MRI studies in patients with brain tumors: a feasibility study.

Background: Transient hypoxia-induced deoxyhemoglobin (dOHb) has recently been shown to represent a comparable contrast to gadolinium-based contrast agents for generating resting perfusion measures in healthy subjects. Here, we investigate the feasibility of translating this non-invasive approach to patients with brain tumors. Methods: A computer-controlled gas blender was used to induce transient precise isocapnic lung hypoxia and thereby transient arterial dOHb during echo-planar-imaging acquisition in a cohort of patients with different types of brain tumors (n = 9). We calculated relative cerebral blood volume (rCBV), cerebral blood flow (rCBF), and mean transit time (MTT) using a standard model-based analysis. The transient hypoxia induced-dOHb MRI perfusion maps were compared to available clinical DSC-MRI. Results: Transient hypoxia induced-dOHb based maps of resting perfusion displayed perfusion patterns consistent with underlying tumor histology and showed high spatial coherence to gadolinium-based DSC MR perfusion maps. Conclusion: Non-invasive transient hypoxia induced-dOHb was well-tolerated in patients with different types of brain tumors, and the generated rCBV, rCBF and MTT maps appear in good agreement with perfusion maps generated with gadolinium-based DSC MR perfusion.

Endovascular embolization as a stand-alone treatment of head and neck paragangliomas with long-term tumor control.

BACKGROUND AND PURPOSE: The impact of therapeutic embolization as a stand-alone treatment of head and neck paragangliomas considered surgically high-risk remains insufficiently understood. The aim of this study was to investigate the procedural risks and long-term volumetric development in head and neck paragangliomas with high surgical risk following therapeutic endovascular embolization as stand-alone treatment. MATERIALS AND METHODS: A retrospective database review of patients who underwent endovascular embolization as primary treatment for head and neck paragangliomas lacking appropriate curative treatment options at our institution (from January 2000 to February 2023) was conducted. Tumor volumetric analyses were performed before embolization and during follow-up. To assess the changes in tumor volume over time, the measurements were performed after embolization, first at 6 months and then on a yearly basis up to 6 years (mean follow-up time was: 33.7 ± 24.4 months). Subgroup analyses were conducted for vagal and jugular/jugulotympanic paragangliomas. RESULTS: A total of 32 head and neck paragangliomas in 28 patients (mean age, 56.1 years ± 16.5 [standard deviation]; 18 female) with therapeutic embolization as stand-alone treatment were evaluated, of which 11 were vagal paragangliomas, 15 jugular/jugulotympanic paragangliomas and 6 carotid body tumors. After a mean follow-up duration of 33.7 ± 24.4 months tumor control was achieved in 75%, with significant median tumor volume reduction at 6 months (p = .02, n = 21). Vagal paragangliomas responded the most to embolization with a significantly decreased median volume from 22.32 cm3; to 19.09 cm3 (p = .008, n = 8). Transient complications occurred in 3.4%. CONCLUSIONS: Therapeutic embolization as a stand-alone treatment offers a low-risk control of tumor growth in surgically high-risk lesions, with a significant reduction in tumor volume after treatment. Among the different subtypes, vagal paragangliomas exhibited the strongest and longest regression of the tumor volume.ABBREVIATIONS: HNPGL = head and neck paragangliomas; IQR = interquartile range; JTP = jugular/jugulotympanic paragangliomas; PVA = polyvinyl alcohol; VP = vagal paragangliomas.

The volume of steal phenomenon is associated with neurological deterioration in patients with large-vessel occlusion minor stroke not eligible for thrombectomy.

INTRODUCTION: A significant number of patients who present with mild symptoms following large-vessel occlusion acute ischemic stroke (LVO-AIS) are currently considered ineligible for EVT. However, they frequently experience neurological deterioration during hospitalization. This study aimed to investigate the association between neurological deterioration and hemodynamic impairment by assessing steal phenomenon derived from blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) in this specific patient cohort. PATIENTS AND METHODS: From the database of our single-center BOLD-CVR observational cohort study (June 2015-October 2023) we retrospectively identified acute ischemic stroke patients with admission NIHSS < 6, a newly detected large vessel occlusion of the anterior circulation and ineligible for EVT. Neurological deterioration during hospitalization as well as outcome at hospital discharge were rated with NIHSS score. We analyzed the association between these two outcomes and BOLD-CVR-derived steal phenomenon volume through regression analysis. Additionally, we investigated the discriminatory accuracy of steal phenomenon volume for predicting neurological deterioration. RESULTS: Forty patients were included in the final analysis. Neurological deterioration occurred in 35% of patients. In the regression analysis, a strong association between steal phenomenon volume and neurological deterioration (OR 4.80, 95% CI 1.32-31.04, p = 0.04) as well as poorer NIHSS score at hospital discharge (OR 3.73, 95% CI 1.52-10.78, p = 0.007) was found. The discriminatory accuracy of steal phenomenon for neurological deterioration prediction had an AUC of 0.791 (95% CI 0.653-0.930). DISCUSSION: Based on our results we may distinguish two groups of patients with minor stroke currently ineligible for EVT, however, showing hemodynamic impairment and exhibiting neurological deterioration during hospitalization: (1) patients exhibiting steal phenomenon on BOLD-CVR imaging as well as hemodynamic impairment on resting perfusion imaging; (2) patients exhibiting steal phenomenon on BOLD-CVR imaging, however, no relevant hemodynamic impairment on resting perfusion imaging. CONCLUSION: The presence of BOLD-CVR derived steal phenomenon may aid to further study hemodynamic impairment in patients with minor LVO-AIS not eligible for EVT.

Absent leptomeningeal collateralization is associated with greatest benefit from mechanical thrombectomy in the 6-24 hour time window.

INTRODUCTION: The impact of leptomeningeal collateralization on the efficacy of mechanical thrombectomy (MT) in patients with anterior circulation large vessel occlusion (aLVO) presenting in the 6-24 h time window remains poorly elucidated. PATIENTS AND METHODS: Retrospective multicenter study of aLVO patients presenting between 6 and 24 h after stroke onset who received MT plus Best Medical Treatment (BMT) or BMT alone. Leptomeningeal collateralization was assessed using single-phase computed tomography angiography (grade 0: no filling; grade 1: filling ⩽50%; grade 2: filling >50% but <100%; grade 3: filling 100% of the occluded territory). Inverse probability of treatment weighted ordinal regression was performed to assess the association between treatment and shift of the modified Rankin Scale (mRS) score toward lower categories at 3 months. We used interaction analysis to explore differential treatment effects on functional outcomes (probabilities for each mRS subcategory at 3 months) at different collateral grades. RESULTS: Among 363 included patients, 62% received MT + BMT. Better collateralization was associated with better functional outcomes at 3 months in the BMT alone group (collateral grade 1 vs 0: acOR 5.06, 95% CI 2.33-10.99). MT + BMT was associated with higher odds of favorable functional outcome at 3 months (acOR 1.70, 95% CI 1.11-2.62) which was consistent after adjustment for collateral status (acOR 1.54, 95% CI 1.01-2.35). Regarding treatment effect modification, patients with absent collateralization had higher probabilities for a mRS of 0-4 and a lower mortality at 3 months for the MT + BMT group. DISCUSSION AND CONCLUSION: In the 6-to-24-h time window, aLVO patients with absent leptomeningeal collateralization benefit most from MT + BMT, indicating potential advantages for this group despite their poorer baseline prognosis.

Dynamic Perviousness Predicts Revascularization Success in Acute Ischemic Stroke.

BACKGROUND: The predictive value of thrombus perviousness in acute ischemic stroke (AIS), as measured by computed tomography (CT), has been intensively studied with conflicting results. In this study, we investigate the predictive potential of the novel concept of dynamic perviousness using three-dimensional (3D) volumetric evaluation of occlusive thrombi. METHODS: The full thrombus volume in 65 patients with a hyperdense artery sign on non-contrast CT (NCCT), who underwent mechanical thrombectomy (MT), was segmented. Perviousness maps were computed voxel-wise for the entire thrombus volume as thrombus attenuation increase (TAI) between NCCT and CT angiography (CTA) as well as between CTA and late venous phase CT (CTV). Perviousness was analyzed for its association with NIHSS at admission, Thrombolysis In Cerebral Infarction (TICI) score, and number of MT passes. RESULTS: The mean late-uptake TAI of thrombi with NIHSS scores greater than 21 at admission was approximately 100% higher than for lower scored NIHSS (p between 0.05 and 0.005). Concerning revascularization results, thrombi requiring less than four MT passes had ca. 80% higher group mean late-uptake TAI than clots requiring four or more passes (p = 0.03), and thrombi with TICI score III had ca. 95% higher group mean late-uptake TAI than thrombi with TICI II (p = 0.03). Standard perviousness showed no significant correlation with MT results. CONCLUSION: Standard thrombus perviousness of 3D clot volume is not associated with revascularization results in AIS. In contrast, dynamic perviousness assessed with a voxel-wise characterization of 3D thrombi volume may be a better predictor of MT outcomes than standard perviousness.

Autoimmune encephalitis: Early and late findings on serial MR imaging and correlation to treatment timepoints.

Introduction: MRI is negative in a large percentage of autoimmune encephalitis cases or lacks findings specific to an antibody. Even rarer is literature correlating the evolution of imaging findings with treatment timepoints. We aim to characterize imaging findings in autoimmune encephalitis at presentation and on follow up correlated with treatment timepoints for this rare disease. Methods: A full-text radiological information system search was performed for "autoimmune encephalitis" between January 2012 and June 2022. Patients with laboratory-identified autoantibodies were included. MRI findings were assessed in correlation to treatment timepoints by two readers in consensus. For statistical analysis, cell-surface vs intracellular antibody groups were assessed for the presence of early limbic, early extralimbic, late limbic, and late extralimbic findings using the χ2 test. Results: Thirty-seven patients (female n = 18, median age 58.8 years; range 25.7 to 82.7 years) with 15 different autoantibodies were included in the study. Twenty-three (62%) patients were MRI-negative at time of presentation; 5 of these developed MRI findings on short-term follow up. Of the 19 patients with early MRI findings, 9 (47%) demonstrated improvement upon treatment initiation (7/9 cell-surface group). There was a significant difference (p = 0.046) between the MRI spectrum of cell-surface vs intracellular antibody syndromes as cell-surface antibody syndromes demonstrated more early classic findings of limbic encephalitis and intracellular antibody syndromes demonstrated more late extralimbic abnormalities. Conclusion: MRI can be used to help narrow the differential diagnosis in autoimmune encephalitis and can be used as a monitoring tool for certain subtypes of this rare disease.

Increased Risk of Recurrent Stroke in Symptomatic Large Vessel Disease With Impaired BOLD Cerebrovascular Reactivity.

BACKGROUND: Impaired cerebrovascular reactivity (CVR) has been correlated with recurrent ischemic stroke. However, for clinical purposes, most CVR techniques are rather complex, time-consuming, and lack validation for quantitative measurements. The recent adaptation of a standardized hypercapnic stimulus in combination with a blood-oxygenation-level-dependent (BOLD) magnetic resonance imaging signal as a surrogate for cerebral blood flow offers a potential universally comparable CVR assessment. We investigated the association between impaired BOLD-CVR and risk for recurrent ischemic events. METHODS: We conducted a retrospective analysis of patients with symptomatic cerebrovascular large vessel disease who had undergone a prospective hypercapnic-challenged BOLD-CVR protocol at a single tertiary stroke referral center between June 2014 and April 2020. These patients were followed up for recurrent acute ischemic events for up to 3 years. BOLD-CVR (%BOLD signal change per mm Hg CO2) was calculated on a voxel-by-voxel basis. Impaired BOLD-CVR of the affected (ipsilateral to the vascular pathology) hemisphere was defined as an average BOLD-CVR, falling 2 SD below the mean BOLD-CVR of the right hemisphere in a healthy age-matched reference cohort (n=20). Using a multivariate Cox proportional hazards model, the association between impaired BOLD-CVR and ischemic stroke recurrence was assessed and Kaplan-Meier survival curves to visualize the acute ischemic stroke event rate. RESULTS: Of 130 eligible patients, 28 experienced recurrent strokes (median, 85 days, interquartile range, 5-166 days). Risk factors associated with an increased recurrent stroke rate included impaired BOLD-CVR, a history of atrial fibrillation, and heart insufficiency. After adjusting for sex, age group, and atrial fibrillation, impaired BOLD-CVR exhibited a hazard ratio of 10.73 (95% CI, 4.14-27.81; P<0.001) for recurrent ischemic stroke. CONCLUSIONS: Among patients with symptomatic cerebrovascular large vessel disease, those exhibiting impaired BOLD-CVR in the affected hemisphere had a 10.7-fold higher risk of recurrent ischemic stroke events compared with individuals with nonimpaired BOLD-CVR.

Leptomeningeal collaterals regulate reperfusion in ischemic stroke and rescue the brain from futile recanalization.

Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many stroke patients recover poorly. Leptomeningeal collaterals (LMCs) are pial anastomotic vessels with yet-unknown functions. We applied laser speckle imaging, ultrafast ultrasound, and two-photon microscopy in a thrombin-based mouse model of stroke and fibrinolytic treatment to show that LMCs maintain cerebral autoregulation and allow for gradual reperfusion, resulting in small infarcts. In mice with poor LMCs, distal arterial segments collapse, and deleterious hyperemia causes hemorrhage and mortality after recanalization. In silico analyses confirm the relevance of LMCs for preserving perfusion in the ischemic region. Accordingly, in stroke patients with poor collaterals undergoing thrombectomy, rapid reperfusion resulted in hemorrhagic transformation and unfavorable recovery. Thus, we identify LMCs as key components regulating reperfusion and preventing futile recanalization after stroke. Future therapeutic interventions should aim to enhance collateral function, allowing for beneficial reperfusion after stroke.

Sustainable reduction of phone-call interruptions by 35% in a medical imaging department using an automatic voicemail and custom call redirection system.

BACKGROUND: Have you ever been in the trenches of a complicated study only to be interrupted by a not-so urgent phone-call? We were, repeatedly- unfortunately. PURPOSE: To increase productivity of radiologists by quantifying the main source of interruptions (phone-calls) to the workflow of radiologists, and too assess the implemented solution. MATERIALS AND METHODS: To filter calls to the radiology consultant on duty, we introduced an automatic voicemail and custom call redirection system. Thus, instead of directly speaking with radiology consultants, clinicians were to first categorize their request and dial accordingly: 1. Inpatient requests, 2. Outpatient requests, 3. Directly speak with the consultant radiologist. Inpatient requests (1) and outpatient requests (2) were forwarded to MRI technologists or clerks, respectively. Calls were monitored in 15-minute increments continuously for an entire year (March 2022 until and including March 2023). Subsequently, both the frequency and category of requests were assessed. RESULTS: 4803 calls were recorded in total: 3122 (65 %) were forwarded to a radiologist on duty. 870 (18.11 %) concerned inpatients, 274 (5.70 %) outpatients, 430 (8.95 %) dialed the wrong number, 107 (2.23 %) made no decision. Throughout the entire year the percentage of successfully avoided interruptions was relatively stable and fluctuated between low to high 30 % range (Mean per month 35 %, Median per month 34.45 %). CONCLUSIONS: This is the first analysis of phone-call interruptions to consultant radiologists in an imaging department for 12 continuous months. More than 35 % of requests did not require the input of a specialist trained radiologist. Hence, installing an automated voicemail and custom call redirection system is a sustainable and simple solution to reduce phone-call interruptions by on average 35 % in radiology departments. This solution was well accepted by referring clinicians. The installation required a one-time investment of only 2h and did not cost any money.

Flow-augmentation STA-MCA bypass for acute and subacute ischemic stroke due to internal carotid artery occlusion and the role of advanced neuroimaging with hemodynamic and flow-measurement in the decision-making: preliminary data.

Background: A major clinical challenge is the adequate identification of patients with acute (<1 week) and subacute (1-6 weeks) ischemic stroke due to internal carotid artery (ICA) occlusion who could benefit from a surgical revascularization after a failure of endovascular and/or medical treatment. Recently, two novel quantitative imaging modalities have been introduced: (I) quantitative magnetic resonance angiography (qMRA) with non-invasive optimal vessel analysis (NOVA) for quantification of blood flow in major cerebral arteries (in mL/min), and (II) blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging to assess cerebrovascular reactivity (CVR). The aim of this study is to present our cohort of patients who underwent surgical revascularization in the acute and subacute phase of ischemic stroke as well as to demonstrate the importance of hemodynamic and flow assessment for the decision-making regarding surgical revascularization in patients with acute and subacute stroke and ICA-occlusion. Methods: Symptomatic patients with acute and subacute ischemic stroke because of persistent ICA-occlusion despite optimal medical/endovascular recanalization therapy who were treated at the Neuroscience Clinical Center of the University Hospital Zurich underwent both BOLD-CVR and qMRA-NOVA to study the hemodynamic and collateral vessel status. Patients selected for surgical revascularization according to our previously published flowchart were included in this prospective cohort study. Repeated NOVA and BOLD-CVR investigations were done after bypass surgery as follow up as well as clinical follow up. Continuous BOLD-CVR and qMRA-NOVA variables were compared using paired Student t-test. Results: Between May 2019 and September 2022, superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery was performed in 12 patients with acute and subacute stroke because of ICA-occlusion despite of optimal endovascular and/or medical treatment prior to the surgery. Impaired BOLD-CVR in the occluded vascular territory [MCA territory: ipsilateral vs. contralateral: -0.03±0.07 vs. 0.11±0.07 %BOLD/mmHgCO2, P<0.001] as well as reduced hemispheric flow with qMRA-NOVA (ipsilateral vs. contralateral: 228.00±54.62 vs. 384.50±70.99 mL/min, P=0.01) were measured indicating insufficient collateralization. Post-operative qMRA-NOVA showed improved hemispheric flow (via bypass) (pre-bypass vs. post-bypass: 236.60±76.45 vs. 334.20±131.33 mL/min, P=0.02) and the 3-month-follow-up with BOLD-CVR showed improved cerebral hemodynamics (MCA territory: pre-bypass vs. post-bypass: -0.01±0.05 vs. 0.06±0.03 %BOLD/mmHgCO2, P=0.02) in all patients studied. Conclusions: Quantitative assessment with BOLD-CVR and qMRA-NOVA allows us to evaluate the pre- and post-operative cerebral hemodynamics and collateral vessel status in patients with acute/subacute stroke due to ICA occlusion who may benefit from surgical revascularization after failure of endovascular/medical treatment.

Ongoing Geometric Remodeling of the Parent Artery After Flow-Diverter Stent Reconstruction in Cerebral Aneurysms: The Device Design Matters.

OBJECTIVE: Configuration changes of the parent artery (PA) after flow-diverter (FD) stent reconstruction, caused by the bending force of the device, may have an additional role in aneurysm occlusion as a result of the secondary alteration of intra-aneurysmal hemodynamics related to the geometry alteration of the vessel. To determine the degree of PA deformation and aneurysm occlusion rates after deployment of 2 different types of FD. METHODS: Patients treated with 2 different designs of cobalt-chromium braid (48 and 64 wire braid) structure FD were subject to analysis. Vascular angle changes at the level of the reconstructed segment immediately after FD deployment and at 1 year follow-up were measured and the potential relationship with aneurysmal occlusion rate was analyzed. RESULTS: Forty-two patients harboring 48 aneurysms were included in the present study. The aneurysms were divided into side wall (85.4%) and bifurcation types (14.6%). Twenty-six aneurysms were treated using the Pipeline FD (48 wire braid; 54.2%) and 22 using the Evolve FD (64 wire braid; 45.8%). Of the 48 aneurysms, 42 (87.5%) met the primary end point of complete occlusion at 12 months. The median postdeployment angle change was 7.04°± 4.59° for the Pipeline and 5.05°± 2.49° for the Evolve, whereas the median 12 months follow-up angle change was 15.49°± 10.99° and 10.01°± 8.83°, respectively. PA angle changes were significantly higher in the bifurcation group compared with the side wall group both during procedure and at 12 months follow-up. Angle change had a statistically nonsignificant association with complete aneurysm occlusion. CONCLUSIONS: PA deformation starts immediately after deployment and remodeling continues for 1 year after. Aneurysms located in the vessel bifurcation were more prone to PA straightening after FD deployment than were side wall aneurysms. Furthermore, Pipeline seemed to be more prone to inducing vascular deformation, compared with Evolve.

The split apparent diffusion coefficient sign: A novel magnetic resonance imaging biomarker for cortical pathology with possible implications in autoimmune encephalitis.

INTRODUCTION: MRI is the imaging modality of choice for assessing patients with encephalopathy. In this context, we discuss a novel biomarker, the "split ADC sign," where the cerebral cortex demonstrates restricted diffusion (high DWI signal and low ADC) and the underlying white matter demonstrates facilitated diffusion (high or low DWI signal and high ADC). We hypothesize that this sign can be used as a biomarker to suggest either acute encephalitis onset or to raise the possibility of an autoimmune etiology. MATERIALS AND METHODS: A full-text radiological information system search of radiological reports was performed for all entities known to produce restricted diffusion in the cortex excluding stroke between January 2012 and June 2022. Initial MRI studies performed upon onset of clinical symptoms were screened for the split ADC sign. RESULTS: 25 subjects were encountered with a positive split ADC sign (15 female; median age = 57 years, range 18-82). Diagnosis included six herpes simplex encephalitis, three peri-ictal MRI changes, eight PRES, two MELAS, and six autoimmune (3 anti-GABAAR, two seronegative, and one anti-Ma2/Ta). Subjects were imaged at a mean 1.8 days after the onset of symptoms (range 0-8). DISCUSSION: We present a novel visual MRI biomarker, the split ADC sign, and highlight its potential usefulness in subjects with encephalopathy to suggest acute disease onset or to raise the possibility of an autoimmune etiology when location-based criteria are applied. When positive, the sign was present on the initial MRI and can therefore be used to help focus further clinical and laboratory workup.

Effectiveness of the preventive administration of vasoactive amines in counterbalancing significant patient blood pressure drops following nimodipine administration during mechanical thrombectomy procedures.

BACKGROUND: Focal vasospasm (FV) of the occluded vessel can occur during the endovascular treatment of acute ischemic stroke (AIS). Nimodipine is commonly used to treat vasospasm and can play a role in distinguishing it from artery narrowing due to iatrogenic dissection or residual clot. However, nimodipine administration can result in arterial hypotension and subsequent enlargement of the ischemic core. OBJECTIVE: To assess the efficacy of preventive and continuous vasoactive amine infusion to counterbalance nimodipine-induced hypotension. METHODS: We reviewed data from a prospective registry of patients treated for AIS between January 2019 and January 2022 who were administered nimodipine. All patients were equipped with an arterial cannula for invasive blood pressure measurement and given vasoactive amines preemptively before general anesthesia and throughout the procedure. Data obtained from invasive monitoring of mean arterial blood pressure (MABP) in a time-lapse of 25 min before and after nimodipine administration were analyzed. RESULTS: MABP significantly decreased after nimodipine administration but remained within the recommended range (81.79 ± 0.49 mmHg). Nimodipine was effective in reducing FV caused by stent retriever passage in 76.3% of cases. Furthermore, it proved valuable in diagnosing iatrogenic dissection (9.2%), residual clot (10.5%), or intracranial stenosis (4%). CONCLUSIONS: Infusion of vasoactive amines effectively counteracted the intraarterial nimodipine effect, thus avoiding frank arterial hypotension during endovascular treatment. Nimodipine has been useful in differentiating the diagnosis of FV resulting from mechanical thrombectomy and other potential causes, such as iatrogenic dissection or residual clot.

Cytotoxic lesions of the corpus callosum: a systematic review.

OBJECTIVES: Cytotoxic lesions of the corpus callosum (CLOCC) are a common magnetic resonance imaging (MRI) finding associated with various systemic diseases including COVID-19. Although an increasing number of such cases is reported in the literature, there is a lack of systematic evidence summarizing the etiology and neuroimaging findings of these lesions. Thus, the aim of this systematic review was to synthesize the applied nomenclature, neuroimaging and clinical features, and differential diagnoses as well as associated disease entities of CLOCC. MATERIALS AND METHODS: A comprehensive literature search in three biomedical databases identified 441 references, out of which 324 were eligible for a narrative summary including a total of 1353 patients. RESULTS: Our PRISMA-conform systematic review identifies a broad panel of disease entities which are associated with CLOCC, among them toxic/drug-treatment-associated, infectious (viral, bacterial), vascular, metabolic, traumatic, and neoplastic entities in both adult and pediatric individuals. On MRI, CLOCC show typical high T2 signal, low T1 signal, restricted diffusion, and lack of contrast enhancement. The majority of the lesions were reversible within the follow-up period (median follow-up 3 weeks). Interestingly, even though CLOCC were mostly associated with symptoms of the underlying disease, in exceptional cases, CLOCC were associated with callosal neurological symptoms. Of note, employed nomenclature for CLOCC was highly inconsistent. CONCLUSIONS: Our study provides high-level evidence for clinical and imaging features of CLOCC as well as associated disease entities. CLINICAL RELEVANCE STATEMENT: Our study provides high-level evidence on MRI features of CLOCC as well as a comprehensive list of disease entities potentially associated with CLOCC. Together, this will facilitate rigorous diagnostic workup of suspected CLOCC cases. KEY POINTS: • Cytotoxic lesions of the corpus callosum (CLOCC) are a frequent MRI feature associated with various systemic diseases. • Cytotoxic lesions of the corpus callosum show a highly homogenous MRI presentation and temporal dynamics. • This comprehensive overview will benefit (neuro)radiologists during diagnostic workup.

The Brainbox-a tool to facilitate correlation of brain magnetic resonance imaging features to histopathology.

Magnetic resonance imaging (MRI) has limitations in identifying underlying tissue pathology, which is relevant for neurological diseases such as multiple sclerosis, stroke or brain tumours. However, there are no standardized methods for correlating MRI features with histopathology. Thus, here we aimed to develop and validate a tool that can facilitate the correlation of brain MRI features to corresponding histopathology. For this, we designed the Brainbox, a waterproof and MRI-compatible 3D printed container with an integrated 3D coordinate system. We used the Brainbox to acquire post-mortem ex vivo MRI of eight human brains, fresh and formalin-fixed, and correlated focal imaging features to histopathology using the built-in 3D coordinate system. With its built-in 3D coordinate system, the Brainbox allowed correlation of MRI features to corresponding tissue substrates. The Brainbox was used to correlate different MR image features of interest to the respective tissue substrate, including normal anatomical structures such as the hippocampus or perivascular spaces, as well as a lacunar stroke. Brain volume decreased upon fixation by 7% (P = 0.01). The Brainbox enabled degassing of specimens before scanning, reducing susceptibility artefacts and minimizing bulk motion during scanning. In conclusion, our proof-of-principle experiments demonstrate the usability of the Brainbox, which can contribute to improving the specificity of MRI and the standardization of the correlation between post-mortem ex vivo human brain MRI and histopathology. Brainboxes are available upon request from our institution.

Blood Oxygenation Level-Dependent Cerebrovascular Reactivity-Derived Steal Phenomenon May Indicate Tissue Reperfusion Failure After Successful Endovascular Thrombectomy.

In acute ischemic stroke due to large-vessel occlusion (LVO), the clinical outcome after endovascular thrombectomy (EVT) is influenced by the extent of autoregulatory hemodynamic impairment, which can be derived from blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR). BOLD-CVR imaging identifies brain areas influenced by hemodynamic steal. We sought to investigate the presence of steal phenomenon and its relationship to DWI lesions and clinical deficit in the acute phase of ischemic stroke following successful vessel recanalization.From the prospective longitudinal IMPreST (Interplay of Microcirculation and Plasticity after ischemic Stroke) cohort study, patients with acute ischemic unilateral LVO stroke of the anterior circulation with successful endovascular thrombectomy (EVT; mTICI scale ≥ 2b) and subsequent BOLD-CVR examination were included for this analysis. We analyzed the spatial correlation between brain areas exhibiting BOLD-CVR-associated steal phenomenon and DWI infarct lesion as well as the relationship between steal phenomenon and NIHSS score at hospital discharge.Included patients (n = 21) exhibited steal phenomenon to different extents, whereas there was only a partial spatial overlap with the DWI lesion (median 19%; IQR, 8-59). The volume of steal phenomenon outside the DWI lesion showed a positive correlation with overall DWI lesion volume and was a significant predictor for the NIHSS score at hospital discharge.Patients with acute ischemic unilateral LVO stroke exhibited hemodynamic steal identified by BOLD-CVR after successful EVT. Steal volume was associated with DWI infarct lesion size and with poor clinical outcome at hospital discharge. BOLD-CVR may further aid in better understanding persisting hemodynamic impairment following reperfusion therapy.

Comparison of clinically available dynamic susceptibility contrast post processing software to differentiate progression from pseudoprogression in post-treatment high grade glioma.

INTRODUCTION: The purpose of this retrospective study was to compare two, widely available software packages for calculation of Dynamic Susceptibility Contrast (DSC) perfusion MRI normalized relative Cerebral Blood Volume (rCBV) values to differentiate tumor progression from pseudoprogression in treated high-grade glioma patients. MATERIAL AND METHODS: rCBV maps processed by Siemens Syngo.via (Siemens Healthineers) and Olea Sphere (Olea Medical) software packages were co-registered to contrast-enhanced T1 (T1-CE). Regions of interest based on T1-CE were transferred to the rCBV maps. rCBV was calculated using mean values and normalized using contralateral normal- appearing white matter. The Wilcoxon test was performed to assess for significant differences, and software-specific optimal rCBV cutoff values were determined using the Youden index. Interrater reliability was evaluated for two raters using the intraclass correlation coefficient. RESULTS: 41 patients (18 females; median age = 59 years; range 21-77 years) with 49 new or size-increasing post-treatment contrast-enhancing lesions were included (tumor progression = 40 lesions; pseudoprogression = 9 lesions). Optimal rCBV cutoffs of 1.31 (Syngo.via) and 2.40 (Olea) were significantly different, with an AUC of 0.74 and 0.78, respectively. Interrater reliability was 0.85. DISCUSSION: We demonstrate that different clinically available MRI DSC-perfusion software packages generate significantly different rCBV cutoff values for the differentiation of tumor progression from pseudoprogression in standard-of-care treated high grade gliomas. Physicians may want to determine the unique value of their perfusion software packages on an institutional level in order to maximize diagnostic accuracy when faced with this clinical challenge. Furthermore, combined with implementation of current DSC-perfusion recommendations, multi-center comparability will be improved.

Resolving the Smoking Paradox: No Evidence for Smoking-Induced Preconditioning in Large Vessel Occlusion Stroke.

INTRODUCTION: Smoking is an established risk factor for stroke. However, several studies have reported a better outcome after stroke for patients who smoke. According to this "smoking paradox" hypothesis, smoking might promote less severe strokes, higher collateral scores, and smaller infarct cores. METHODS: In this retrospective study, we screened data of 2,980 acute ischemic stroke patients with MCA-M1 occlusion treated with mechanical thrombectomy. Patients were categorized according to smoking status (current, former, or never). We assessed univariate associations between clinical characteristics and smoking status. Subsequently, we used adjusted regression analysis to evaluate associations of smoking with stroke severity on admission (National Institutes of Health Stroke Scale [NIHSS]; primary endpoint), infarct core volume, and collateral status (secondary endpoints). RESULTS: Out of 320 patients, 19.7% (n = 63) were current smokers and 18.8% (n = 60) were former smokers. Admission NIHSS, reperfusion success, and modified Rankin Scale (mRS) after 3-6 months were similar in all groups. Current smokers were younger, more often male and less likely to have atrial fibrillation compared to former and never smokers. In regression analyses, smoking status was neither associated with admission NIHSS (estimate 0.54, 95% confidence interval [CI]: -1.27-2.35, p = 0.557) nor with collateral status (estimate 0.79, 95% CI: 0.44-1.44, p = 0.447) or infarct core volume (estimate -0.69, 95% CI: -15.15-13.77, p = 0.925 for current vs. never smokers). CONCLUSION: We could not confirm the smoking paradox. Our results support the fact that smoking causes stroke at a younger age, highlighting the role of smoking as a modifiable vascular risk factor.

Ultra-High-Resolution Time-of-Flight MR-Angiography for the Noninvasive Assessment of Intracranial Aneurysms, Alternative to Preinterventional DSA?

PURPOSE: The 3D time-of-flight (TOF) magnetic resonance angiography (MRA) at 3T shows high sensitivity for intracranial aneurysms but is inferior to three-dimensional digital subtraction angiography (3D-DSA) regarding aneurysm characteristics. We applied an ultra-high-resolution (UHR) TOF-MRA using compressed sensing reconstruction to investigate the diagnostic performance in preinterventional evaluation of intracranial aneurysms compared to conventional TOF-MRA and 3D-DSA. METHODS: In this study 17 patients with unruptured intracranial aneurysms were included. Aneurysm dimensions, configuration, image quality and sizing of endovascular devices were compared between conventional TOF-MRA at 3T and UHR-TOF with 3D-DSA as gold standard. Quantitatively, contrast-to-noise ratios (CNR) were compared between TOF-MRAs. RESULTS: On 3D-DSA, 25 aneurysms in 17 patients were detected. On conventional TOF, 23 aneurysms were detected (sensitivity: 92.6%). On UHR-TOF, 25 aneurysms were detected (sensitivity: 100%). Image quality was not significantly different between TOF and UHR-TOF (p = 0.17). Aneurysm dimension measurements were significantly different between conventional TOF (3.89 mm) and 3D-DSA (4.2 mm, p = 0.08) but not between UHR-TOF (4.12 mm) and 3D-DSA (p = 0.19). Irregularities and small vessels at the aneurysm neck were more frequently correctly depicted on UHR-TOF compared to conventional TOF. Comparison of the planned framing coil diameter and flow-diverter (FD) diameter revealed neither a statistically significant difference between TOF and 3D-DSA (coil p = 0.19, FD p = 0.45) nor between UHR-TOF and 3D-DSA (coil: p = 0.53, FD 0.33). The CNR was significantly higher in conventional TOF (p = 0.009). CONCLUSION: In this pilot study, ultra-high-resolution TOF-MRA visualized all aneurysms and accurately depicted aneurysm irregularities and vessels at the base of the aneurysm comparably to DSA, outperforming conventional TOF. UHR-TOF with compressed sensing reconstruction seems to represent a non-invasive alternative to pre-interventional DSA for intracranial aneurysms.

A dual-center validation of the PIRAMD scoring system for assessing the severity of ischemic Moyamoya disease.

Background: Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD) is a recently proposed imaging-based scoring system that incorporates the severity of disease and its impact on parenchymal hemodynamics in order to better support clinical management and evaluate response to intervention. In particular, PIRAMD may have merit in identifying symptomatic patients that may benefit most from revascularization. Our aim was to validate the PIRAMD scoring system. Methods: Patients with ischemic Moyamoya disease, who underwent catheter angiographic [modified Suzuki Score (mSS) and collateralization status], morphological MRI and a parenchymal hemodynamic evaluation with blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) at two transatlantic centers, were retrospectively included. The primary outcome was the presence of neurological symptoms. The diagnostic capacity of each PIRAMD feature alone was evaluated, as well as combined and the inter-institutional differences of each parameter were evaluated. Results: Seventy-two hemispheres of 38 patients were considered for analysis, of which 39 (54%) were classified as symptomatic. The presence of a prior infarct had the highest odds ratio [odds ratio (OR) =24; 95% CI: 6.7-87.2] for having neurological symptoms, followed by impaired CVR (OR =17; 95% CI: 5-62). No inter-institutional differences in the odds ratios or area under the curve (AUC) were found for any study parameter. The PIRAMD score had an AUC of 0.88 (95% CI: 0.80-0.96) with a similar AUC for the PIRAMD grading score. Conclusions: Our multicentric validation of the recently published PIRAMD scoring system was highly effective in rating the severity of ischemic Moyamoya disease with excellent inter-institutional agreement. Future studies should investigate the prognostic value of this novel imaging-based score in symptomatic patients with Moyamoya disease.